Transcriptional Regulatory Element Functional Genomics Equipment

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Over the past 13 years I have established an NSERC funded Program for Decoding the Mammalian Regulatory Genome at the University of Toronto that has supported scientific discoveries and training for 84 HQP. I am requesting a comprehensive system for Transcriptional Regulatory Element Functional Genomics. This system will allow for an expansion of our current approach from cells to a whole organism. Without this equipment, my NSERC funded research program and associated HQP training will be severely impacted. Research supported by this system aims to uncover the regulatory mechanisms that govern mammalian genome function using both computational and functional genomics approaches. Despite completion of the human genome sequence almost 20 years ago we are currently not able to determine the function of the vast majority of this sequence. We understand how to read the sequence code within gene coding regions but these are 98% of the genome are gene regulatory elements that turn genes on/off in specific cells. Although we know gene regulatory elements are important for the proper development of complex organisms and are often the cause of specific differences in the body plan of different species, we know remarkably little about the sequence code that gives them their function. This is like having a book written in a language you can't read. Or, as we have fully sequenced genomes for more than 100 mammals, an entire library of books that you can't read. The requested system for Transcriptional Regulatory Element Functional Genomics includes a data analysis workstation, real-time PCR machine, chilled centrifuge for sample preparation and a mouse embryo electroporation device. This equipment is critical to my research program and the training of HQP. At the moment our work is able to investigate gene expression in cells but not in whole mammalian organisms. The requested equipment will allow us to investigate gene regulatory elements that are functional in specific tissues during development. In the long term, fully decoding genome sequences will allow us to predict how regulatory sequence changes can affect the expression of specific genes. This will have widespread impact on our understanding of development, evolution and the underlying cause of phenotype variation in populations.